It has long been desired to increase the rate of growth in meat-producing animals as well as to enhance the quality of the meat derived therefrom, especially as regards the proportion of lean to fat in such meat. Progress has, of course, been made to this end by the hybridization of various meat producing animals and in formulating improved feed compositions with a view to achieving an increase in the rate of growth of the animal and the efficiency of the conversion of its feed, i.e., the ratio of unit weight of meat produced per unit quantity of feed consumed, but little hope appears to exist for further major progress along these lines.
Another long-recognized approach adopted for male meat-producing mammals is castration of animals usually at an early stage in their development for the purpose of achieving a kind of feminization of the male animal while simultaneously eliminating its normal aggressive behavior and sexual activity. More recently, castration has been combined with hormone administration typically accomplished by a continuous release hormonal implant inserted, for instance, in the ear of the castrated animal at an age typically of 2-3 months. The the quantity of the hormone and the rate of its release from the implant, as determined by the composition of the implant, are so designed as to achieve a gradual and continual release of the hormone into the animal's system and so correlated with the rate of metabolism of the hormone in the animal's system that the quantity of hormone remaining in the ultimate meat obtained after slaughter was sufficiently small as to satisfy applicable government standards. While castration alone or combined with a hormone implant has some beneficial consequences on the ultimate meat production in terms of increased weight production and thus better feed efficiency, much of the improvement is in the form of increased fat, e.g., a higher ratio of fat to lean which, of course, offsets the overall improvement by reduced meat quality.
Considerable research has been done by the present applicants, their associates, and others in the field of hormones in order to acquire a better understanding of the enormously complex changes that are involved in hormone secretion in animals and the effects of such secretion in various animal species. Extensive studies have been applied to such animals such as fish, chicken, pig and ruminants such as deer. Thus, it has been described how the adenohypophyseal cells of teleost fish, chicken, rats and pigs respond to gonadal steroids administered during embryogenesis, the neonatal or "critical" period, the adult stage, and during old age. This research was done by V. R. Pantic in "Synthesis and Release of Adenohypophyseal Hormones", Plenum Press, N. Y. 1980 (M. Jutisz and K. W. McKerns, eds.) pp. 335-362. Gonadotropic cells that secrete FSH and LH were found to be suppressed, while prolactin and growth stimulating cells were increased. The effects were most pronounced during embryogenesis and the neonatal critical period. These studies were continued, with the emphasis on prolactin target cells, by V. R. Pantic, in "Regulation of Target Cell Responsiveness", Vol 2, Plenum Press, N.Y. 1984 (K. W. McKerns, A. Aakvaag and V. Hansson, eds.) pp 283-295. Further, it has been shown by F. C. Bancroft, P. R. Dobner and Li-Yuan Yu, in "Synthesis and Release of Adenohypophyseal Hormones", Plenum Press, N.Y. 1980 (M. Jutisz and K. W. McKerns, eds.) pp. 311-333;that glucocorticoids induce pregrowth hormone messenger RNA. A description has been provided how prolactin, growth hormone, and chorionic somatomammotropin are derived from a common evolutionary ancester protein. All are lactogenic and growth promoting: W. L. Miller and S. W. Mellon, in "Regulation of Gene Expression, Plenum Press, N.Y. 1983 (K. W. McKerns, ed.) pp. 177-202. During evolution the genes for these hormones migrated to separate cell types and are under complex regulatory processes.
The complexity of hormonal effects and the difficulty of predicting the consequences of the same is illustrated by the different and even opposite effects that are often obtained according to the amount and the duration of the administration of a given hormone as well as the period of such administration in the development of the animal. For example, a low-level constant administration may continually suppress a particular function; a single higher does may initially suppress that function, followed by a rebound increase. The suppression of adrenal cortex secretion by estrogen, followed by a marked rebound increase in adrenal glucocorticoid secretion has been described by K. W. McKerns in "The Regulation of Adrenal Function by Estrogens and Other Hormones", Biochemica Et Biophysica Acta, 71 (1963) 710-718.
From the information obtained during studies such as the above as well as subsequent unpublished research, it has been discovered, quite remarkably, that the administration of a female gonadal steroidal hormone to meat producing animals if applied to the animal before its sexual maturation, and preferably quite early, especially during its neonatal period, a surprising and entirely unexpected selective response is induced by which the sexual maturation of the animal, e.g., achievement of the gonadal function such as spermatogenesis in males and development of secondary sex characteristics is suppressed or retarded while the growth function and anabolic effect of the animal is enhanced and made more efficient. Those knowledgeable in endocrinology have traditionally believed that sexual maturation, e.g., spermatogenesis in the male, the development of secondary sexual characteristics, including the development of the seminal glandular system of the animal, and release of androgen and growth hormone prolactin complex to achieve a growthanabolic effect in male animals occurred together in the natural maturation of the animal. Thus, castration would obviously prevent spermatogenesis and the development of secondary sexual characteristics but with a consequential reduction in the release of androgen and its anabolic effect and the growth hormone-prolactin effect so that growth production was channeled more toward fat rather than muscle or lean meat.
In the practice of the present invention, an unexpected and surprisingly selective or differential response has been found, by which spermatogensis and secondary sexual development are temporarily suppressed or blocked while simultaneously androgen and growth hormone-prolactin production, as manifested, for example, by the level of the male gonadal hormone testosterone is not only not suppressed but remains at least comparable to, if not higher than, that taking place in similar untreated animals. As a consequence, the animal can be brought to its normal slaughter weight at a time significantly earlier than is required for untreated or intact animals or castrated animals. The conversion of the feed by the animal during the growth period up to slaughter, which is its most rapid growth period, takes place at a significantly more efficient rate, as measured in terms of unit weight of meat derived per unit weight of feed consumed. Further, the proportion of fat is reduced so that a leaner meat product having a higher ratio of lean to fat is obtained giving a significantly higher meat quality. The characteristics of the meat in other respects such as flavor, tenderness, texture and so on do not appear to be adversely affected by the practice of the present method and remain at least as acceptable as, if not better than, those of meat obtained from untreated animals, including castrates.
Additional benefits have also been observed in some species notably the pig. Sexual maturation in the male pig occurs, on the average, at around five months and is manifested by aggressive behavior and sexual activity such as fighting with other males and attempted mountings. As the secondary sexual characteristics become fully developed, the seminal system becomes operative resulting in the strong odor characteristic of boars and this strongly oderiferous seminal fluid permeates the tissue of the animal causing its meat to be tainted for most human consumption. Male pigs treated according to the present invention do not exhibit such aggressive behavior and are free from the obnoxious scent and meat flavor of untreated male pigs.
The reality of the improvements described above has been theoretically confirmed by histological testing of the treated animals compared with untreated animals. Thus, the present method has been shown to lead to induction, proliferation and increased gene expression of growth and prolactin cells in the pituitary that secrete growth hormone, growth factors and prolactin hormone. Prolactin has both a growth stimulating effect and a gonad suppressing effect. Pituitary gonadotrophs that secrete folicle stimulating hormones (FHS) and luteinizing hormones (LH) appear to be suppressed in number and function. The pro-opioidcorticotropin cells appear to be increased. Incereased endorphins (and other opioid compounds) from these cells may have a sedative-tranquilizing effect on the animals. Increased corticotropin (ACTH) enlarges the vascular and reticular zone of the adrenal cortex and increases glucocorticoid and androgen production.
More specifically, taking the pig as an example, it was observed histologically by the light microscope and the electron microscope that growth hormone and prolactin cell types in the pig pituitary were increased, as were cells that secrete pro-ACTH-endorphin. On the other hand, gonadotropin cells that secrete FSH and LH were decreased.